Methods for treatment of cancer with an anti-tigit antagonist antibody

Patent metadata

Field	Value
Publication number	US-2022016243-A1
Application number	US-202117159128-A
Country	US
Kind code	A1
Filing date	Jan 26, 2021
Priority date	Jan 27, 2020
Publication date	Jan 20, 2022
Grant date	—

Abstract

The present invention relates to methods, uses, and compositions for the treatment of cancer (e.g., a lung cancer; a cervical cancer; a breast cancer; a head and neck cancer; a liver cancer; a bladder cancer; a gastric cancer; an esophageal cancer; a pancreatic cancer; a kidney or renal cancer; a melanoma; an ovarian cancer; or a colorectal cancer). More specifically, the invention concerns the treatment of patients having cancer with an anti-TIGIT antagonist antibody, including treatment with an anti-TIGIT antagonist antibody in a combination therapy.

First claim

1 - 503 . (canceled)

504 . A method of treating a subject or population of subjects having a lung cancer, the method comprising administering to the subject or population of subjects a dosing regimen comprising one or more dosing cycles of an effective amount of an anti-TIGIT antagonist antibody, a PD-1 axis binding antagonist, a platinum-based chemotherapeutic agent, and a topoisomerase II inhibitor, wherein the treatment extends progression-free survival (PFS) or overall survival (OS) of the subject as compared to treatment with the PD-1 axis binding antagonist, the platinum-based chemotherapeutic agent, and the topoisomerase II inhibitor without the anti-TIGIT antagonist antibody.

505 . The method of claim 504 , wherein the anti-TIGIT antagonist antibody, PD-1 axis binding antagonist, platinum-based chemotherapeutic agent, and topoisomerase II inhibitor are administered in each of four initial dosing cycles.

506 . The method of claim 504 , wherein the anti-TIGIT antagonist antibody and the PD-1 axis binding antagonist are further administered in one or more additional cycles following the fourth initial dosing cycle.

507 . The method of claim 504 , wherein the platinum-based chemotherapeutic agent and the topoisomerase II inhibitor are omitted from each of the one or more additional dosing cycles.

508 . The method of claim 504 , wherein the platinum-based chemotherapeutic agent is carboplatin and the topoisomerase II inhibitor is etoposide.

509 . The method of claim 504 , wherein the lung cancer is extensive stage small cell lung cancer (ES-SCLC).

510 . The method of claim 509 , wherein the subject or subjects are treatment-naïve for ES-SCLC and/or wherein the subject or subjects do not have a presence or history of brain metastases.

511 . The method of claim 504 , wherein the anti-TIGIT antagonist antibody is a monoclonal antibody and/or a human antibody.

512 . The method of claim 504 , wherein (a) the anti-TIGIT antagonist antibody is a full-length antibody or (b) the anti-TIGIT antagonist antibody is an antibody fragment that binds TIGIT selected from the group consisting of Fab, Fab′, Fab′-SH, Fv, single chain variable fragment (scFv), and (Fab′) 2 fragments.

513 . The method of claim 504 , wherein the anti-TIGIT antagonist antibody has intact Fc-mediated effector function.

514 . The method of claim 504 , wherein:
(a) the anti-TIGIT antagonist antibody is tiragolumab, vibostolimab, etigilimab, or EOS084448; (b) the anti-TIGIT antagonist antibody comprises the following hypervariable regions (HVRs):
an HVR-H1 sequence comprising the amino acid sequence of SNSAAWN (SEQ ID NO: 1);
an HVR-H2 sequence comprising the amino acid sequence of KTYYRFKWYSDYAVSVKG (SEQ ID NO: 2);
an HVR-H3 sequence comprising the amino acid sequence of ESTTYDLLAGPFDY (SEQ ID NO: 3);
an HVR-L1 sequence comprising the amino acid sequence of KSSQTVLYSSNNKKYLA (SEQ ID NO: 4);
an HVR-L2 sequence comprising the amino acid sequence of WASTRES (SEQ ID NO: 5); and
an HVR-L3 sequence comprising the amino acid sequence of QQYYSTPFT (SEQ ID NO: 6);
(c) the anti-TIGIT antagonist antibody comprises a VH domain comprising the amino acid sequence of SEQ ID NO: 17 and a VL domain comprising the amino acid sequence of SEQ ID NO: 19; and/or (d) the anti-TIGIT antagonist antibody comprises a VH domain comprising the amino acid sequence of SEQ ID NO: 18 and a VL domain comprising the amino acid sequence of SEQ ID NO: 19.

515 . The method of claim 504 , wherein the PD-1 axis binding antagonist is selected from the group consisting of a PD-L1 binding antagonist, a PD-1 binding antagonist, and a PD-L2 binding antagonist.

516 . The method of claim 515 , wherein the PD-1 axis binding antagonist is an anti-PD-L1 antagonist antibody.

517 . The method of claim 516 , wherein:
(a) the anti-PD-L1 antagonist antibody is atezolizumab, MDX-1105, durvalumab, avelumab, SHR-1316, CS1001, envafolimab, TQB2450, ZKAB001, LP-002, CX-072, IMC-001, KL-A167, APL-502, cosibelimab, lodapolimab, FAZ053, TG-1501, BGB-A333, BCD-135, AK-106, LDP, GR1405, HLX20, MSB2311, RC98, PDL-GEX, KD036, KY1003, YBL-007, or HS-636; (b) the anti-PD-L1 antagonist antibody comprises the following HVRs:
an HVR-H1 sequence comprising the amino acid sequence of GFTFSDSWIH (SEQ ID NO: 20);
an HVR-H2 sequence comprising the amino acid sequence of AWISPYGGSTYYADSVKG (SEQ ID NO: 21);
an HVR-H3 sequence comprising the amino acid sequence of RHWPGGFDY (SEQ ID NO: 22);
an HVR-L1 sequence comprising the amino acid sequence of RASQDVSTAVA (SEQ ID NO: 23);
an HVR-L2 sequence comprising the amino acid sequence of SASFLYS (SEQ ID NO: 24); and
an HVR-L3 sequence comprising the amino acid sequence of QQYLYHPAT (SEQ ID NO: 25);
and/or (c) the anti-PD-L1 antagonist antibody comprises a VH domain comprising the amino acid sequence of SEQ ID NO: 26 and a VL domain comprising the amino acid sequence of SEQ ID NO: 27.

518 . The method of claim 516 , wherein the anti-PD-L1 antagonist antibody is a monoclonal antibody and/or a humanized antibody.

519 . The method of claim 516 , wherein the anti-PD-L1 antagonist antibody is (a) a full-length antibody or (b) an antibody fragment that binds PD-L1 selected from the group consisting of Fab, Fab′, Fab′-SH, Fv, scFv, and (Fab′) 2 fragments.

520 . The method of claim 515 , wherein the PD-1 axis binding antagonist is an anti-PD-1 antagonist antibody.

521 . The method of claim 504 , wherein the method comprises:
(a) administering to the subject or population of subjects the anti-TIGIT antagonist antibody at a dose of (i) between about 500 mg to about 700 mg every three weeks or (ii) about 600 mg every three weeks and/or administering to the subject or population of subjects the PD-1 axis binding antagonist at a dose of (i) between about 900 mg to about 1500 mg every three weeks or (ii) about 1200 mg every three weeks; (b) administering to the subject or population of subjects the anti-TIGIT antagonist antibody at a dose of (i) about 700 mg to about 1000 mg every four weeks or (ii) about 840 mg every four weeks and/or administering to the subject or population of subjects the PD-1 axis binding antagonist at a dose of (i) about 1400 mg to 2000 mg every four weeks or (ii) about 1680 mg every four weeks; or (c) administering to the subject or population of subjects the anti-TIGIT antagonist antibody at a dose of (i) about 300 mg to about 600 mg every two weeks or (ii) about 420 mg every two weeks and/or administering to the subject or population of subjects the PD-1 axis binding antagonist at a dose of (i) between about 600 mg to about 1200 mg every two weeks or (ii) about 840 mg every two weeks.

522 . The method of claim 504 , wherein the method comprises (a) administering to the subject or population of subjects the PD-1 axis binding antagonist before the anti-TIGIT antagonist antibody; (b) administering to the subject or population of subjects the anti-TIGIT antagonist antibody before the PD-1 axis binding antagonist; or (c) administering to the subject or population of subjects the PD-1 axis binding antagonist simultaneously with the anti-TIGIT antagonist antibody.

523 . A method of treating a subject or population of subjects having a lung cancer, the method comprising administering to the subject or population of subjects a dosing regimen comprising one or more dosing cycles of an anti-TIGIT antagonist antibody, a PD-1 axis binding antagonist, a first chemotherapeutic agent which is a platinum-based chemotherapeutic

Assignees

• Genentech Inc
• Hoffmann La Roche

Inventors

• Lai Catherine
• Lau Janet
• Lee Anthony Jongha
• Li Shi
• Lin-Liu Yvonne Gail
• Matheny Christina Jeanne
• Mendus Diana
• Meng Raymond D
• Nguyen Duc Anh
• Patel Jilpa Bhupendra
• Pham Thinh Quang
• Rooney Isabelle Anne
• Stevens Heather Blythe
• Troutman Sarah Marie
• Wang Lijia
• Wang Yulei
• Williams Patrick Georges Robert
• Wu Benjamin
• Yan Yibing
• Zhang Aijing
• Zhang Xiaosong
• Ballinger Marcus Dale
• Barak Hila
• Bennett Elizabeth Alexandra
• Castro Marcela Lucia
• Cha Edward Namserk
• Chan Hui Min Phyllis
• Chui Stephen
• Cotter Christopher Roland
• Degaonkar Viraj Vinay
• Gitlitz Barbara Jennifer
• Hoang Tien
• Komatsubara Kimberly Mayumi

Classifications

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61K31/675

  having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate · CPC title

• C07K2317/24

  containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered · CPC title

• C07K16/2827

  against B7 molecules, e.g. CD80, CD86 · CPC title

• A61K31/337

  having four-membered rings, e.g. taxol · CPC title